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Background <p>Trophoblast cell surface antigen 2 (Trop-2) is a targetable transmembrane glycoprotein commonly overexpressed in breast cancer (BC). This study combines a systematic review and meta-analysis with a retrospective analysis of an independent early BC patient cohort, aiming to investigate the expression patterns of Trop-2 and their clinical significance in BC.</p> Methods <p>A systematic literature search was conducted up to October 2025 to identify studies evaluating Trop-2 protein expression levels and clinical outcomes in patients with BC receiving Trop-2–directed antibody-drug conjugates (ADCs) or chemotherapy. Random-effects meta-analyses were performed to estimate pooled Trop-2 positivity rates and to assess progression-free (PFS) and overall survival (OS) across Trop-2 expression levels. Additionally, an association analysis between Trop-2 protein and gene expression was performed in an early BC patient cohort (n = 564) using immunohistochemistry and gene expression data. Trop-2 protein expression was assessed using both conventional observer-based methods and digital quantitative image analysis.</p> Results <p>A total of 41 studies fulfilled the inclusion criteria. The overall pooled Trop-2 protein positivity rate was 72% [95% Confidence Interval (CI), 67–77%; 41 studies, n = 9170]. Trop-2–directed ADCs improved PFS versus chemotherapy across different H-score groups, with the greatest benefit in tumours with high H-score [3 studies; n = 575; Hazard Ratio (HR) = 0.33, 95% CI 0.20–0.56, p &lt; 0.0001]. For OS, the benefit was observed in the low H-score group (2 studies; n = 272; HR = 0.75, 95% CI 0.57–0.98, p = 0.034). In the study cohort, Trop-2 protein by observer-read assessment was detected in 396/454 patients (87.22%). Digital pathology identified 54 (11.90%) tumours with low, 326 (71.80%) with medium, and 74 (16.30%) with high H-scores. Observer-read and digital assessments were significantly associated (Pearson’s chi-square test, p &lt; 0.001). Higher Trop-2 protein and gene expression were associated with worse distant recurrence-free interval (HR<sub>adj</sub> = 1.45, 95% CI 1.01–2.08, p = 0.04 and HR<sub>adj</sub> = 1.33, 95% CI 1.05–1.68, p = 0.02, respectively), particularly in Luminal B subtype.</p> Conclusions <p>Trop-2 was detectable across all BC subtypes, exhibiting a wide range of expression levels. Our study suggests that Trop-2 may have a potential prognostic significance in early BC.</p>

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Assessment of Trophoblast cell surface antigen 2 (Trop-2) expression and its clinical significance in breast cancer: a multi-level analysis of protein and gene expression

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  • 发表日期：

    2026年7月31日

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  • Maria Angeliki Toli,
  • Michail Sarafidis,
  • Panagiotis Filis,
  • Evangelos Tzoras,
  • Nikolaos Tsiknakis,
  • Emmanouil Sifakis,
  • Efstathia Liatsou,
  • Georgios Rassidakis,
  • Jonas Bergh,
  • Alexios Matikas,
  • Ioannis Zerdes,
  • Theodoros Foukakis

摘要

Background

Trophoblast cell surface antigen 2 (Trop-2) is a targetable transmembrane glycoprotein commonly overexpressed in breast cancer (BC). This study combines a systematic review and meta-analysis with a retrospective analysis of an independent early BC patient cohort, aiming to investigate the expression patterns of Trop-2 and their clinical significance in BC.

Methods

A systematic literature search was conducted up to October 2025 to identify studies evaluating Trop-2 protein expression levels and clinical outcomes in patients with BC receiving Trop-2–directed antibody-drug conjugates (ADCs) or chemotherapy. Random-effects meta-analyses were performed to estimate pooled Trop-2 positivity rates and to assess progression-free (PFS) and overall survival (OS) across Trop-2 expression levels. Additionally, an association analysis between Trop-2 protein and gene expression was performed in an early BC patient cohort (n = 564) using immunohistochemistry and gene expression data. Trop-2 protein expression was assessed using both conventional observer-based methods and digital quantitative image analysis.

Results

A total of 41 studies fulfilled the inclusion criteria. The overall pooled Trop-2 protein positivity rate was 72% [95% Confidence Interval (CI), 67–77%; 41 studies, n = 9170]. Trop-2–directed ADCs improved PFS versus chemotherapy across different H-score groups, with the greatest benefit in tumours with high H-score [3 studies; n = 575; Hazard Ratio (HR) = 0.33, 95% CI 0.20–0.56, p < 0.0001]. For OS, the benefit was observed in the low H-score group (2 studies; n = 272; HR = 0.75, 95% CI 0.57–0.98, p = 0.034). In the study cohort, Trop-2 protein by observer-read assessment was detected in 396/454 patients (87.22%). Digital pathology identified 54 (11.90%) tumours with low, 326 (71.80%) with medium, and 74 (16.30%) with high H-scores. Observer-read and digital assessments were significantly associated (Pearson’s chi-square test, p < 0.001). Higher Trop-2 protein and gene expression were associated with worse distant recurrence-free interval (HRadj = 1.45, 95% CI 1.01–2.08, p = 0.04 and HRadj = 1.33, 95% CI 1.05–1.68, p = 0.02, respectively), particularly in Luminal B subtype.

Conclusions

Trop-2 was detectable across all BC subtypes, exhibiting a wide range of expression levels. Our study suggests that Trop-2 may have a potential prognostic significance in early BC.